1. Field of the Invention
The invention relates to the use of sensory G protein-coupled receptor complexes that recognize chemical sensants, particularly those involving olfactory and taste receptors; polypep-tide fragments and mutants thereof; classes of such receptors; polynucleotides encoding such receptors, fragments and mutants thereof, and representatives of receptor classes; genetic vectors including such polynucleotides; and cells and non-human organisms engineered to express such receptor complexes, fragments and mutants of an olfactory or taste receptor, and representatives of receptor classes to simulate sensory perception of odorants and tastants. The invention also relates to the use of such products as a biosensor or component thereof to detect, to identify, to measure, or otherwise process the event of binding between the receptor and its cognate ligand (i.e., chemical sensant). The invention has application, for example, in the design and formu-lation of odorant and tastant compositions.
2. Description of the Related Art
The olfactory and taste systems provide sensory information about the chemical environment. Olfactory receptors and taste receptors recognize, respectively, “odorants” and “tastants,” collectively referred to as “sensants” or “sensory receptor ligands” herein. A “primary” sensant is an odorant or tastant ligand that substantially binds to sensory receptors with a ligand-binding site of a single amino acid sequence. Olfactory and taste receptors belong to the superfamily of seven-transmembrane guanyl nucleotide-binding proteins: such receptors are, however, also recognized as distinct families, or sub-genuses, of olfactory or taste receptors (see Raming Nature 361:353, 1993). These receptors control diverse physiological functions such as media-ting signaling from an external chemical stimulus across the membrane containing the receptor into a cell, endocrine function, exocrine function, heart rate, lipolysis, and carbohydrate metabolism. Thus, the dissection of these diverse functions into component signals is needed.
But the complexities of sensory perception of chemical sensants prevent easy translation of the olfaction and taste systems to a machine sensor. For example, U.S. Pat. Nos. 5,675,070; 5,918,257; 5,928,609; and 6,085,576 disclose machine sensors that use various chemistries, but they do not take advantage of the specificity of olfactory and taste receptors for their cognate ligands to produce a biosensor.
WO 00/15269 discloses methods and apparatus for odor reproduction. The total affinities of a specific odorant with a group of receptors was called the affinity fingerprint of the odorant. This odorant fingerprint was represented by a vector of affinity values. It was proposed to repro-duce an arbitrary odor by inputting its sensed odorant fingerprint into a device, which has a palate of predetermined odorants and produces a composite odor using predetermined odorant finger-prints by minimizing the difference between vectors representing the sensed odorant fingerprint and the predetermined odorant fingerprints. This reference, however, does not teach or suggest the human olfactory receptors disclosed herein.
WO 00/70343 discloses biosensors and sense replication systems using G-protein coupled receptors (GPCR). It was proposed to mimic the response of the G-protein signal transduction system by detecting the affinity of a stimulus to a plurality of GPCR, codifying such information into electronic signals, and reproducing the stimulus by converting the codified information into a combination of stimulant entities. But this reference also does not teach or suggest the human olfactory receptors disclosed herein.
WO 01/27158 discloses olfactory receptors and their use to determine the correspondence between individual odorant receptors and particular odors. It was proposed that the interactions between an odor and olfactory receptors can be used to represent the odor and to re-create it. This reference, however, does not teach or suggest the human olfactory receptors disclosed herein.
Dissecting the function of sensory receptors by binding sensory receptors of a clone of cells expressing a single sensory receptor gene, fragmentation of sensory receptors to provide ligand-binding or signal-transducing domains thereof, and construction of fusion sensory recep-tor proteins will separate the diverse physiological functions associated with sensory perception at the level of ligand-receptor binding. Furthermore, novel “primary sensants” that are identified and isolated by the methods described herein may be used to further define the function of the cognate sensory receptor by uniquely enhancing or, in the alternative, blocking stimulation of sensory receptors with a single ligand-binding domain.
The present invention addresses the need for better understanding of these ligand-receptor interactions by using a large set of identified sensory receptors. Even if the receptor set used is incomplete (i.e., a partial set of all sensory receptors encoded in the genome), a large number of sensants will be detected. Moreover, redundancy in the chemical structures recognized by the sensory receptors or combinatorial processing of signals from different sensory receptors would allow broad coverage of chemically diverse sensants (e.g., by selection of a representative class of sensory receptors). Also provided are, inter alia, methods for utilizing such sensory receptors and biosensors to simulate sensory perception. To analyze ligand-receptor interactions and their effects on cell signaling and the processing of those signals in sensory perception, specific sensants and their cognate receptor complexes are detected, identified, and measured under binding conditions. Fragrances and flavorings can be detected, identified, measured, and/or custom designed by the methods herein described. In addition, drugs that incorporate artificial odors and/or tastes can be formulated.